Diabetes mellitus is a group of metabolic disorders caused by islet dysfunction, insulin resistance etc. A variety of pathogenic factors, such as genetic factors, immune dysfunction, mental factors, can cause diabetes. According to the statistics of the World Health Organization in 2011, 366 million people had diabetes worldwide. Diabetes has become the third largest disease, following cardio-cerebrovascular diseases and malignant tumors. China has been the world's biggest diabetes country with a prevalence rate of 9.7%, which is higher than the world's average. With 92.4 million diabetics in total, China is ranking the top in the world.
Now, there are many drugs for the treatment of type II diabetes, including metformin, sulfonylureas, DPP-4 inhibitors, PPARγ agonists, α-glucosidase inhibitors, insulin and GLP-1 analogues, etc. However, the present drugs have some defects, such as insignificant curative effect, and short acting time. Some drugs even have side effects like hypoglycemia, weight gain, edema, fracture, lactic acidosis and gastrointestinal discomfort etc.
Adenosine monophosphate activated protein kinase (AMPK) plays a leading role in the glucolipid metabolism in vivo. It is an energy meter and main metabolic switch that senses and decodes intracellular changes in energy status. AMPK activation can significantly treat the metabolic disorders of type II diabetes, and improve insulin sensitivity in vivo. It has been confirmed as a new target for the treatment of type II diabetes. Clinical drugs with hypoglycemic and lipid-lowering effects, like metformin, TZDs and berberine, have been proved to be able to activate AMPK at the cellular level, which paved a rout for AMPK as a new anti-diabetic drug target.
A class of fatty acid compounds have been designed and synthesized. These compounds have the ability to activate AMPK at the cellular level and inhibit mouse primary hepatocyte glucose output. Some of these compounds exhibit excellent AMPK activation effects, and could significantly stimulate the phosphorylation of AMPK and ACC in a concentration-dependent manner at the cellular level. Most of the compounds had the significantly effect of reducing glucose output. Such compounds have tremendous development potentials as therapeutic drugs for diabetes.